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Innate Lymphoid Cell Aging

先天性淋巴细胞老化

基本信息

批准号：
10531485
负责人：
Qi yang
金额：
$ 22.38万
依托单位：
RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10531485
关键词：
Innate Lymphoid Cell Aging

项目摘要

Project Summary/Abstract Under this administrative supplement, we propose to examine impact of innate lymphoid cell aging on the disease outcome of SARS-CoV-2 infection, by adding COVID-19 to the parent study which examines the innate lymphoid cell aging during influenza infection. The aged population is particularly susceptible to COVID-19. It is estimated that more than 80% of individuals who have died from COVID-19 in the U.S. are elderly individuals ≥ 65 years old. The underlying mechanisms remain unclear. Aging is associated drastic and complicated changes in the immune system. Aging is associated drastic and complicated changes in the immune system. The mucosal barrier sites harbor unique subsets of innate and innate-like lymphocytes implicated in host defense, tissue homeostasis, and tissue repair. Our published and preliminary data indicate that the long-lived lung-resident innate/innate-like lymphocytes, such as ILC2 and MAIT cells, undergo tremendous changes with aging. We hypothesize that impaired function of mature lung ILC2 underpins tissue damage and inflammation observed during SARS-CoV-2 infection with aging, and that boosting the activity of ILC2 will increase host resistance and tolerance to severe COVID-19 in the elderly individuals. We have recently established a mouse model of SARS-CoV-2 infection in aged mice. We will further characterize this mouse model, and will use this model to test whether enhancing ILC2 activity will increase host resistance and tolerance resistance to COVID-19 in aged mice. We have available for this study a CDC approved full functioning ABSL3 lab. This supplement will directly address multiple objectives related to the goals outlined in the COVID-19 notice of special interest. This supplement will develop aged animal models suitable for studies on pathogenesis of SARS-CoV-2 infection in the aging context. The proposal experiments will also elucidate how cellular and molecular mechanisms of aging impact the treatment, recovery, and repair of tissue and organ systems during SARS-CoV-2 infection.

项目概要/摘要根据本行政补充，我们建议检查先天淋巴细胞的影响通过将 COVID-19 添加到父代中，衰老对 SARS-CoV-2 感染疾病结果的影响研究检查流感感染期间先天淋巴细胞的老化。老年人人群特别容易感染 COVID-19。据估计，80%以上在美国死于 COVID-19 的人是 ≥ 65 岁的老年人。这根本机制仍不清楚。衰老与剧烈而复杂的变化有关免疫系统。衰老与免疫系统剧烈而复杂的变化有关系统。粘膜屏障部位含有独特的先天和先天样淋巴细胞亚群参与宿主防御、组织稳态和组织修复。我们已发布的和初步的数据表明，长寿命肺驻留先天/先天样淋巴细胞，例如 ILC2 和 MAIT细胞随着衰老发生巨大的变化。我们假设功能受损成熟的肺 ILC2 是 SARS-CoV-2 期间观察到的组织损伤和炎症的基础感染会随着衰老而增加，而增强ILC2的活性会增加宿主的抵抗力，老年人对严重 COVID-19 的耐受性。我们最近建立了一个鼠标老年小鼠 SARS-CoV-2 感染模型。我们将进一步表征该小鼠模型，并将使用该模型来测试增强ILC2活性是否会增加宿主抵抗力以及老年小鼠对 COVID-19 的耐受性。我们为这项研究提供了 CDC 经批准的功能齐全的 ABSL3 实验室。该补充将直接解决多个目标与特别关注的 COVID-19 通知中概述的目标相关。本补充将开发适合研究 SARS-CoV-2 感染发病机制的老年动物模型老龄化背景。该提案的实验还将阐明细胞和分子如何衰老机制影响组织和器官系统的治疗、恢复和修复 SARS-CoV-2 感染期间。